Process of synthesizing N-acyl auxiliaries

ABSTRACT

A process of synthesizing N-acyl auxiliary compounds is disclosed. A compound of the formula: ##STR1## is reacted with an anhydride in the presence of a lithium salt and an amine base to produce the N-acylated auxiliary.

BACKGROUND OF THE INVENTION

Chiral auxiliaries have been extensively used in asymmetric syntheses.Traditionally, N-acyl 2-oxazolidinones have been synthesized bylithiating the oxazolidinone with n-butyl lithium at -78° C., followedby acylating with an acyl chloride. N-acyl sultams have similarly beensynthesized by deprotonation with NaH, followed by N-acylation with anacyl chloride. Such two step procedures have been used to convert theoxazolidinone or sultam to the respective trimethylsilyl derivatives,followed by reaction with excess acyl chloride in refluxing toluene.Neither of these synthesis schemes is particularly useful when the acylside chain contains substituent groups that are reactive. Also, thesereactions take an inordinately long time to run to completion. Thepresent invention overcomes the disadvantages in these processes.

When deptotonation is effected with a strong base, followed by acylationusing an acid chloride or anhydride, side reactions frequently occur ifthe substrate contains other functional groups.

Copending application Ser. No. 281,394, filed on Jul. 27, 1994 addressesthe N-acylation of oxazolidinones and 2,10-sultams. The presentapplication addresses the N-acylation of other ring systems.

SUMMARY OF THE INVENTION

A process of synthesizing an N-acyl auxiliary compound of the formula:##STR2## is disclosed.

R and R' independently represent members selected from the groupconsisting of:

(a) --C₁₋₆ alkyl, --C₂₋₆ alkenyl or --C₂₋₆ alkynyl;

(b) --C₁₋₆ alkyl, --C₂₋₆ alkenyl or --C₂₋₆ alkynyl substituted with from1-3 groups selected from: --NH₂ ; --OH; --COOH, --COO(C₁₋₄) alkyl,--OC₁₋₄ alkyl; --C(O)--C₁₋₄ alkyl; --OC(O)C₁₋₄ alkyl; --NH(C₁₋₆ alkyl);--NH(C₂₋₆ alkenyl); --NH(C₂₋₆ alkynyl); --N(C₁₋₆ alkyl)₂ ; --N(C₂₋₆alkenyl)₂ ; --N(C₂₋₆ alkynyl)₂ ; --OC(O)NH₂ ; --OC(O)NHC₁₋₄ alkyl;--OC(O)N(C₁₋₄ alkyl)₂ ; -aryl; -heteroaryl; --C₃₋₈ cycloalkyl;-heterocyclyl; -halo; --NHC(O)OC₁₋₆ alkyl; --N(C₁₋₄ alkyl)C(O)OC₁₋₆alkyl, and -aryl, heteroaryl, C₃₋₈ cycloalkyl or heterocyclylsubstituted with from 1-3 groups selected from halo, hydroxy, --C₁₋₄alkyl, --C₁₋₄ alkoxy, hydroxy-C₁₋₄ alkyl, -amino, --NH(C₁₋₄ alkyl) and--N(C₁₋₄ alkyl)₂ ;

(c) aryl, heteroaryl, C₃₋₈ cycloalkyl or heterocyclyl, unsubstituted orsubstituted with from 1-3 groups selected from halo, hydroxy, C₁₋₄alkoxy, hydroxy-C₁₋₄ alkyl, amino, C₁₋₄ alkylamino, and di-C₁₋₄alkylamino;

(d) C₁₋₆ alkyl, C₂₋₆ alkenyl or C₂₋₆ alkynyl substituted with

(1) 1 to 3 groups selected from: --NHP; --NP₂ ; --OP; --CO₂ P; --NP(C₁₋₆alkyl); --NP(C₂₋₆ alkenyl); --NP(C₂₋₆ alkynyl); --OC(O)NHP; --OC(O)NP₂ ;OC(O)NP(C₁₋₆ alkyl); --NPC(O)O(C₁₋₆ alkyl); aryl, heteroaryl, C₃₋₈cycloalkyl or heterocyclyl substituted with from 1-3 groups selectedfrom --OP, --C₁₋₃ alkyl-OP, --NHP, --NP₂, --C₁₋₃ alkyl-NHP, --C₁₋₃alkyl-NP₂, --NP--C₁₋₃ alkyl, and 0-3 members selected from the groupconsisting of: halo, C₁₋₃ alkyl, C₁₋₃ alkoxy, and --N(C₁₋₃ alkyl)₂ ;

and

(2) 0 to 3 groups selected from the group consisting of: --COO(C₁₋₃)alkyl, --OC₁₋₄ alkyl; --C(O)--C₁₋₄ alkyl; --N(C₁₋₆ alkyl)₂ ; --N(C₂₋₆alkenyl)₂ ; --N(C₂₋₆ alkynyl)₂ ; --OC(O)N(C₁₋₄ alkyl)₂ ; aryl;heteroaryl; C₃₋₈ cycloalkyl; heterocyclyl; halo; --N(C₁₋₃alkyl)C(O)OC₁₋₆ alkyl; and aryl, heteroaryl, --C₃₋₈ cycloalkyl orheterocyclyl substituted with from 1-3 groups selected from: halo,--C₁₋₃ alkyl, --C₁₋₃ alkoxy and --N(C₁₋₃ alkyl)₂,

and (e) aryl, heteroaryl, C₃₋₈ cycloalkyl or heterocyclyl substitutedwith:

(1) from 1 to 3 members selected from the group consisting of: --OP,--C₁₋₄ alkyl-OP, --NHP, --NP₂, --C₁₋₄ alkyl-NHP, --C₁₋₄ alkyl-NP₂ and--NPC₁₋₄ alkyl,

and

(2) from 0 to 3 members selected from the group consisting of: halo,--C₁₋₄ alkoxy and --N(C₁₋₄ alkyl)₂ ;

wherein P represents a protecting group, and n represents an integer offrom 2 through 7.

A compound of the formula: ##STR3## wherein R' and n are as definedabove, is reacted with an anhydride represented by the formula: ##STR4##wherein each R is the same or different, and is as previously defined,in the presence of a lithium salt and an amine base to produce: ##STR5##

DETAILED DESCRIPTION OF THE INVENTION

As used herein, the following terms and definitions apply unlessotherwise indicated.

The term "alkyl" refers to a monovalent alkane (hydrocarbon) derivedradical containing from 1 to 6 carbon atoms unless otherwise defined. Itmay be straight or branched. Preferred alkyl groups include methyl,ethyl, propyl, isopropyl, butyl and t-butyl. When substituted, alkylgroups may be substituted with up to four substituent groups, at anyavailable point of attachment. When the alkyl group is said to besubstituted with an alkyl group, this is used interchangeably with"branched alkyl group".

Alkylidene refers to a divalent group --(CH₂)₂₋₅ --. When the alkylideneis substituted, the substituent groups can be at any available point ofattachment. All stereoconfigurations at asymmetric carbon atoms areincluded in the invention.

The term "alkoxy" refers to a C₁₋₄ alkoxy radical: --OC₁₋₄ alkyl. Thepreferred alkoxy group is methoxy.

Cycloalkyl is a specie of alkyl, containing from 3 to 15 carbon atoms,preferably 3-8 carbon atoms, without alternating or resonating doublebonds between carbon atoms. It may contain from 1 to 4 rings which arefused. The preferred cycloalkyl groups are cyclopentyl and cyclohexyl.

When a bond is indicated by a wavy line, this means that thestereoconfiguration is contemplated. For example, ##STR6## includes thefollowing configurations: ##STR7## Such compounds can be used in pureform or in combination as a mixture of isomers.

The term "alkenyl" refers to a hydrocarbon radical straight, branched orcyclic containing from 2 to 6 carbon atoms and at least one carbon tocarbon double bond. Preferred alkenyl groups include ethenyl, propenyl,butenyl and cyclohexenyl.

The term "alkynyl" refers to a hydrocarbon radical straight or branched,containing from 2 to 6 carbon atoms and at least one carbon to carbontriple bond. Preferred alkynyl groups include ethynyl, propynyl andbutynyl.

Aryl refers to aromatic rings e.g., phenyl, substituted phenyl and likegroups, as well as tings which are fused, e.g., naphthyl, phenanthrenyland the like. An aryl group thus contains at least one ring having atleast 6 atoms, with up to five such tings being present, containing upto 22 atoms therein, with alternating (resonating) double bonds betweenadjacent carbon atoms or suitable heteroatoms. The preferred aryl groupsare phenyl, naphthyl and phenanthrenyl. Aryl groups may likewise besubstituted as defined. Preferred substituted aryls include phenyl andnaphthyl.

The term "heteroatom" means O, S or N selected on an independent basis.

The term "heteroaryl" refers to a monocyclic aromatic hydrocarbon grouphaving 5 or 6 ring atoms, or a bicyclic aromatic group having 8 to 10atoms, containing at least one heteroatom, O, S or N, in which a carbonor nitrogen atom is the point of attachment, and in which one or twoadditional carbon atoms are optionally replaced by a heteroatom selectedfrom O or S, and in which from 1 to 3 additional carbon atoms areoptionally replaced by nitrogen atoms, said heteroaryl group beingoptionally substituted as described herein.

Heteroaryl thus includes aromatic and partially aromatic groups whichcontain one or more heteroatoms. Examples of this type are pyrrole,pyridine, oxazole, thiazole and oxazine. Additional nitrogen atoms maybe present together with the first nitrogen and oxygen or sulfur,giving, e.g., thiadiazole. Preferred heteroaryl groups are thiazolyl,imidazolyl, pyridyl and pyrrolyl.

The term "heterocycloalkyl" refers to a cycloalkyl group (nonaromatic)in which one of the carbon atoms in the ring is replaced by aheteroatom, and in which up to three additional carbon atoms may bereplaced by heteroatoms. Preferred heterocycloalkyl groups includepiperidinyl, pyrrolidinyl and tetrahydrofuranyl.

Halogen and "halo" refer to bromine, chlorine, fluorine and iodine.

The term "lithium salt" is used in the conventional sense, and refers tosubstantially non-basic lithium salts. The following lithium salts arerepresentative: lithium bromide, lithium chloride, lithium fluoride,lithium iodide, lithium perchlorate, lithium nitrate, lithium sulfateand lithium tetrafluoroborate. Preferred salts are lithium chloride andlithium bromide.

Amine bases as used herein refers to triethylamine, pyridine,diisopropylethylamine, lutidine, 1,8-diazobicyclo[5.4.0]undec-7-ene and1,5-diazabicyclo[4.3.0]non-5-ene.

The R and R' groups in many instances are in protected form. When afunctional group is termed "protected", this means that the group is inmodified form to preclude undesired side reactions at the protectedsite. All such variations are included in the presently claimedinvention. Suitable protecting groups for the compounds of the presentinvention will be recognized from the present application taking intoaccount the level of skill in the art, and with reference to standardtextbooks, such as Greene, T. W. et al. Protective Groups in OrganicSynthesis Wiley, New York (1991). Examples of suitable protecting groupsare contained throughout the specification. While the protecting groupsare generally designated by the variable P, different protecting groupsare preferable for different functionalities.

Where hydroxyl is shown in protected form as --OP, this can also bedesignated --OP¹. When a protecting group is present attached to anitrogen atom, as in --NHP, --NP₂ and the like, these protecting groupscan be designated interchangeably as P². Lastly, when a protecting groupis present on a carboxyl group, as in --COOP, such protecting groups canalso be designated interchangeably as P³.

Examples of suitable hydroxyl protecting groups (P¹) which can be usedin the syntheses described herein include the following:t-butylmethoxyphenylsilyl, t-butoxydiphenylsilyl, trimethylsilyl,triethylsilyl, o-nitrobenzyloxycarbonyl, p-nitrobenzyloxycarbonyl,benzyloxycarbonyl, t-butyloxycarbonyl, 2,2,2-trichloroethyloxycarbonyland allyloxycarbonyl. Preferred hydroxyl protecting groups P¹ aretrimethylsilyl and triethylsilyl.

Examples of suitable amino protecting groups (P²) include the following:t-butoxycarbonyl (t-BOC), 2,2,2-trichloroethoxycarbonyl,allyloxycarbonyl, benzyloxycarbonyl, o- and p-nitrobenzyloxycarbonyl.The preferred amino protecting group (P²) is t-BOC.

Examples of suitable carboxyl protecting groups (P³) include thefollowing: benzhydryl, o-nitrobenzyl, p-nitrobenzyl, 2-naphthylmethyl,allyl, 2-chloroallyl, benzyl, 2,2,2-trichloroethyl, trimethylsilyl,t-butyldimethylsilyl, t-butyldiphenylsilyl, 2-(trimethylsilyl)ethyl,phenacyl, p-methoxybenzyl, acetonyl, p-methoxyphenyl, 4-pyridylmethyland t-butyl. A preferred carboxyl protecting group (P³) isp-nitrobenzyl.

The structure ##STR8## contains an amide linkage, the nitrogen atom ofwhich is reacted with the anhydride to form an imide in accordance withthe process described herein. In this structure, n represents an integerfrom 2 to 7. The rings thus can be as follows: ##STR9## The preferredvalues of n are 2, 3 and 4.

In one preferred embodiment of the invention, the lactam is reacted witha mixed anhydride as described below in the presence of a lithium saltand an amine base. The mixed anhydride has the formula R¹--C(O)--O--(O)--R². R¹ and R² are different from each other and areselected from the values of R. Lithium salts which can be used in thisparticular embodiment include the halide salts, e.g., LiCl and LiBr.

Amine bases which are suitable for use herein include triethylamine (Et₃N), pyridine, diisopropylethylamine, lutidine,1,8-diazobicyclo[5.4.0]undec-7-ene and 1,5-diazabicyclo[4.3.0]non-5-ene.The preferred amine base is triethylamine.

In another embodiment of the invention, the anhydride is a symmetricanhydride which contains reactive groups. Thus, the anhydride is of theformula: R--C(O)--O--C(O)--R wherein each R represents a substitutedalkyl group, an alkenyl or substituted alkenyl group, an alkynyl orsubstituted alkynyl group, a substituted aryl group, a substitutedheteroaryl group, a substituted C₃₋₈ cycloalkyl group or a substitutedheterocyclyl group.

A preferred example is acrylic anhydride, which can be reacted with anyof the auxiliaries to perform the N-acylation.

Acylation of the lactam is generally carded out by reacting theanhydride, either mixed or symmetric, with the lactam in the presence ofa lithium salt and the N-containing base in a single reaction vessel.The anhydride can be formed in situ via the reaction of the requisiteacid and an acyl chloride in a non-reactive solvent. Base can beincluded, and the reaction nm at about -20° C. After the anhydride isformed, generally over about 2 hours, the lithium salt (1.1-1.2 eq.) isadded, followed by the lactam. Acylation is typically complete within4-6 hours, after warming to room temperature.

The temperature range for the reaction is about -20° C. to about roomtemperature.

The acylation reaction can be conducted in any appropriate organicsolvent. The preferred solvent for use herein is tetrahydrofuran.

In a preferred embodiment of the invention, a beta lactam is reactedwith the anhydride to produce the N-acylated beta lactam in the presenceof a nitrogen containing base, a substantially non-reactive solvent anda lithium salt. ##STR10## The preferred acylation reaction is carded outin the presence of lithium halide, as necessary for the acylation tooccur.

The invention is further described in connection with the followingnon-limiting examples.

PREPARATIVE EXAMPLE 1 PREPARATION OF ACRYLIC ANHYDRIDE

To a solution of acrylic acid (1.3 equiv.) and Et₃ N (2.5 equiv.) in THFwas added acryloyl chloride (1.2 equiv.) at -20° C. A white solid wasformed. The mixture was stirred at ˜-20° C. for 1 hr to complete thereaction, producing acrylic anhydride 1a.

PREPARATIVE EXAMPLE 2 PREPARATION OF SYMMETRIC AND ASYMMETRIC ANHYDRIDES##STR11##

Using the procedure set forth in Preparative Example 1, anhydrides canbe prepared in accordance with the following table.

                  TABLE 2                                                         ______________________________________                                        Cpd      R.sup.1         R.sup.2                                              ______________________________________                                        2a                                                                                      ##STR12##      (CH.sub.3).sub.3 C                                   3a       t-Boc-NH(CH.sub.2).sub.4                                                                      (CH.sub.3).sub.3 C                                   4a       CH.sub.3 CH.sub.2                                                                             CH.sub.3 CH.sub.2                                    5a                                                                                      ##STR13##                                                                                     ##STR14##                                           6a                                                                                      ##STR15##                                                                                     ##STR16##                                           ______________________________________                                    

EXAMPLE 1 N-PROPIONYL AZETDINONE ##STR17## To a solution of2-azetidinone (1.42 g, 20 mmol), lithium chloride (1.00 g, 23.5 mmol),and triethylamine (2.30 g, 23 mmol) in 100 mL of THF was added propionicanhydride (2.86 g, 22 mmol) at -20° C. The mixture was allowed to warmto 20° C. and stirred for 4 h. THF was removed under reduced pressureand the residue was partitioned between ethyl acetate (60 mL) andaqueous HCl (0.5M, 50 mL). The organic phase was then washed with HCl(0.5M, 50 mL), brine (50 mL), NaHCO₃ (1M, 50 mL), and brine (50 mL). Theorganic solution was dried over sodium sulfate and filtered. Evaporationof the solvent afforded the title compound as a colorless liquid (1.96g).

¹ H NMR (CDCl₃) d 1.15 (t, 3H), 2.70 (q, 2H), 3.05 (t, 2H), 3.60 (t,2H).

EXAMPLE 2 PREPARATION OF N-PROPIONYL PYRROLIDINE ##STR18## To themixture of 2-pyrrolidine (1.70 g, 20 mmol), lithium bromide (2.13 g, 25mmol), triethylamine (2.30 g, 23 mmol) in ethyl acetate (100 mL) wasadded propionic anhydride (2.86 g, 22 mmol) at -20° C. The mixture waswarmed to 20° C. and stirred for 6 h. Aqueous HCl (0.5M, 50 mL) wasadded and the phases were separated. The organic phase was washed withHCl (0.5M, 50 mL), brine (50 mL), NaHCO₃ (1M, 50 mL), and brine (50 mL).The solution was dried over sodium sulfate and filtered. Evaporation ofthe solvent afforded the title compound as a colorless liquid (2.40 g).

¹ H NMR (CDCL₃) d 1.13 (t, 3H), 2.02 (m, 2H), 2.60 (t, 2H), 2.90 (t,2H), 3.80 (t, 2H).

EXAMPLE 3

Using the compounds set forth in Preparative Examples 1 and 2, and theprocedures set forth in Examples 1 and 2, the acylating agent and lactamin columns 1 and 2 of Table 3 are reacted to produce the N-acylatedproduct of column 3.

                                      TABLE 3                                     __________________________________________________________________________    Acylating Agent    Lactam Product                                             __________________________________________________________________________     ##STR19##                                                                                        ##STR20##                                                                            ##STR21##                                          1a                                                                                                ##STR22##                                                                            ##STR23##                                          1a                                                                                                ##STR24##                                                                            ##STR25##                                           ##STR26##                                                                                        ##STR27##                                                                            ##STR28##                                                                    and                                                                            ##STR29##                                          2a                                                                                                ##STR30##                                                                            ##STR31##                                                                    and                                                                            ##STR32##                                          2a                                                                                                ##STR33##                                                                            ##STR34##                                                                    and                                                                            ##STR35##                                           ##STR36##                                                                                        ##STR37##                                                                            ##STR38##                                                                    and                                                                            ##STR39##                                          3a                                                                                                ##STR40##                                                                            ##STR41##                                                                    and                                                                            ##STR42##                                          3a                                                                                                ##STR43##                                                                            ##STR44##                                                                    and                                                                            ##STR45##                                           ##STR46##                                                                                        ##STR47##                                                                            ##STR48##                                          4a                                                                                                ##STR49##                                                                            ##STR50##                                          4a                                                                                                ##STR51##                                                                            ##STR52##                                           ##STR53##                                                                                        ##STR54##                                                                            ##STR55##                                          5a                                                                                                ##STR56##                                                                            ##STR57##                                          5a                                                                                                ##STR58##                                                                            ##STR59##                                           ##STR60##                                                                                        ##STR61##                                                                            ##STR62##                                          6a                                                                                                ##STR63##                                                                            ##STR64##                                          6a                                                                                                ##STR65##                                                                            ##STR66##                                          __________________________________________________________________________

What is claimed is:
 1. A process of synthesizing an N-acyl auxiliarycompound of the formula: ##STR67## wherein: R and R' independentlyrepresent members selected from the group consisting of:(a) --C₁₋₆alkyl, --C₂₋₆ alkenyl or --C₂₋₆ alkynyl; (b) --C₁₋₆ alkyl, --C₂₋₆alkenyl or --C₂₋₆ alkynyl substituted with from 1-3 groups selectedfrom: --NH₂ ; --OH; --COOH, --COO(C₁₋₄) alkyl, --OC₁₋₄ alkyl;--C(O)--C₁₋₄ alkyl; --OC(O)C₁₋₄ alkyl; --NH(C₁₋₆ alkyl); --NH(C₂₋₆alkenyl); --NH(C₂₋₆ alkynyl); --N(C₁₋₆ alkyl)₂ ; --N(C₂₋₆ alkenyl)₂ ;--N(C₂₋₆ alkynyl)₂ ; --OC(O)NH₂ ; --OC(O)NHC₁₋₄ alkyl; --OC(O)N(C₁₋₄alkyl)₂ ; -aryl; -heteroaryl; --C₃₋₈ cycloalkyl; -heterocyclyl; -halo;--NHC(O)OC₁₋₆ alkyl; --N(C₁₋₄ alkyl)C(O)OC₁₋₆ alkyl, and -aryl,heteroaryl, C₃₋₈ cycloalkyl or heterocyclyl substituted with from 1-3groups selected from halo, hydroxy, --C₁₋₄ alkyl, --C₁₋₄ alkoxy,hydroxy-C₁₋₄ alkyl, -amino, --NH(C₁₋₄ alkyl) and --N(C₁₋₄ alkyl)₂ ; (c)aryl, heteroaryl, C₃₋₈ cycloalkyl or heterocyclyl, unsubstituted orsubstituted with from 1-3 groups selected from halo, hydroxy, C₁₋₄alkoxy, hydroxy-C₁₋₄ alkyl, amino, C₁₋₄ alkylamino, and di-C₁₋₄alkylamino; (d) C₁₋₆ alkyl, C₂₋₆ alkenyl or C₂₋₆ alkynyl substitutedwith (1) 1 to 3 groups selected from: --NHP; --NP₂ ; --OP; --CO₂ P;--NP(C₁₋₆ alkyl); --NP(C₂₋₆ alkenyl); --NP(C₂₋₆ alkynyl); --OC(O)NHP;--OC(O)NP₂ ; OC(O)NP(C₁₋₆ alkyl); --NPC(O)O(C₁₋₆ alkyl); aryl,heteroaryl, C₃₋₈ cycloalkyl or heterocyclyl substituted with from 1-3groups selected from --OP, --C₁₋₃ alkyl-OP, --NHP, --NP₂, --C₁₋₃alkyl-NHP, --C₁₋₃ alkyl-NP₂, --NP--C₁₋₃ alkyl, and 0-3 members selectedfrom the group consisting of: halo, C₁₋₃ alkyl, C₁₋₃ alkoxy, and--N(C₁₋₃ alkyl)₂ ;and (2) 0 to 3 groups selected from the groupconsisting of: --COO(C₁₋₃ ) alkyl, --OC₁₋₄ alkyl; --C(O)--C₁₋₄ alkyl;--N(C₁₋₆ alkyl)₂ ; --N(C₂₋₆ alkenyl)₂ ; --N(C₂₋₆ alkynyl)₂ ;--OC(O)N(C₁₋₄ alkyl)₂ ; aryl; heteroaryl; C₃₋₈ cycloalkyl; heterocyclyl;halo; --N(C₁₋₃ alkyl)C(O)OC₁₋₆ alkyl; and aryl, heteroaryl, --C₃₋₈cycloalkyl or heterocyclyl substituted with from 1-3 groups selectedfrom: halo, --C₁₋₃ alkyl, --C₁₋₃ alkoxy and --N(C₁₋₃ alkyl)₂, and (e)aryl, heteroaryl, C₃₋₈ cycloalkyl or heterocyclyl substituted with: (1)from 1 to 3 members selected from the group consisting of: --OP, --C₁₋₄alkyl-OP, --NHP, --NP₂, --C₁₋₄ alkyl-NHP, --C₁₋₄ alkyl-NP₂ and --NPC₁₋₄alkyl,and (2) from 0 to 3 members selected from the group consisting of:halo, --C₁₋₄ alkoxy and --N(C₁₋₄ alkyl)₂ ;wherein P represents aprotecting group, and n represents an integer of from 2 through 7,comprising reacting a compound of the formula: ##STR68## wherein n andR' are as previously defined, with an anhydride represented by theformula: ##STR69## wherein the R groups are the same or different, andare as previously defined, in the presence of a lithium salt and anamine base to produce: ##STR70##
 2. A process in accordance with claim 1wherein a compound of the formula ##STR71## is reacted with an anhydriderepresented by the formula: ##STR72## wherein R and n are as previouslydefined, in the presence of a lithium salt and an amine base to produce:##STR73##
 3. A process in accordance with claim 2 wherein the compound:##STR74## is a member selected from the group consisting of: ##STR75##4. A process in accordance with claim 1 wherein the lithium salt isselected from the group consisting of: lithium bromide, lithiumchloride, lithium fluoride, lithium iodide, lithium perchlorate, lithiumnitrate, lithium sulfate and lithium tetrafluoroborate.